Adipose-derived stem cells contribute to vascular remodeling via Clec11a+ subpopulation

Recent researches identified the existence of adipose derived stem cells (ADSCs) in adipose tissue. Perivascular ADSCs (PV-ADSCs) locate around vasculatures and can differentiate into vascular lineages. However, the detailed cellular heterogeneity within PV-ADSCs has not been investigated. Therefore, we performed single-cell profiling of subcutaneous (S-) and perivascular (PV-) ADSCs from wild-type and obese mice. After referring to the clustering strategies from other ADSCs’ single-cell data, we provided a more comprehensive picture and trajectory, especially for PV-ADSCs. Both single-cell analysis and in vitro experiments revealed that S-ADSCs from obese mice had impaired abilities of cell migration and proliferation compared to wild-type S-ADSCs. PV-ADSCs have distinctively intrinsic properties. We uncovered 4 subpopulations of PV-ADSCs including Dpp4+, Col4a2+, Clec11a+ and Sult1e1+ cells. Notably, the differentiative function of PV-ADSCs towards vascular lineages was mainly attributed to the existence of Clec11a+ subpopulation, which highly expressed Mgp. The present study provided an integrative view of the ADSCs’ variance from the perspective of origins and obesity. We performed single-cell sequencing by applying droplet-based 10X genomics platform for different ADSCs. Perivascular or subcutaneous AT was harvested from either DB/DB or wildtype mice. After the digestion, stromal vascular fraction (SVF) was passed through a 100 μm and then a 70 μm filter to remove any adipocytes and debris. CD45, live/dead staining, DAPI were applied to exclude CD45+ cells, dead cells and erythrocytes.